THE EFFECTS OF PHOTODYNAMIC THERAPY IN BIOLOGICAL SYSTEMS

Abstract: Photodynamic therapy (PDT) is a recent acquisition in the treatment of cutaneous premalignant and malignant lesions, based upon the administration or induction of the synthesis of a photosensitizer in the tumoral tissue, followed by the illumination of the target area using a radiation Photodynamic therapy (PDT) is a modern antineoplastic treatment modality used in numerous medical specialties (dermatology, gastroenterology, urology or ophthalmology). The method consists in administrating or inducing the synthesis of a photosensitizer in the tumoral tissue, followed by the illumination of the target area, using a radiation with an adequate wavelength. The activation of the photosensitizer on this pathway triggers complex photochemical processes, resulting in the production of reactive oxygen species (ROS) that produce extensive tissue destruction and local vascularisation alterations, apoptosis, necrosis and autophagy induction and triggering of the immune response, all of the above contributing to the destruction of tumour cells. For the achievement of the destructive effects of PDT, the concurrent presence of sufficient quantities of photosensitizer and molecular oxygen in the target area is necessary, as well as the use of a light source of an adequate emission spectrum that would correspond to the absorption spectrum of the photosensitizer and, at the same time, it would allow a good tissue penetration of the light to its level, with minimal absorption by other cutaneous chromophores (melanin, oxi/hemoglobin and water). Effects of PDT on tumour vascularisation The anti-tumoral in vivo effects of PDT have a greater amplitude than anticipated considering the hypoxia present in most of the tumours, which suggests the fact that tumour cells are not only destroyed through direct photodynamic effects but also through other mechanisms, most likely through the destruction of blood vessels that supply nutrients to the tumour.(1) The destruction of tumour vascularisation causes the shortage of the nutrition and energetic support needed by the tumour cells, leading to the partial or total destruction of the tumour. The reduction of the blood supply secondary to the vascular destruction is also accompanied by an equivalent decrease of the oxygen quantity delivered to the tumour; the lack of oxygen will lead to the decrease or abolishment of the efficiency of subsequent PDT light pulses as PDT effects are dependent on the production of oxygen reactive species (ROS) in the target area, especially of singlet oxygen, through photochemical processes. Moreover, the photochemical reactions triggered by a light pulse consume the tumour tissular oxygen, emphasizing tumour hypoxia and limiting the photodynamic effect of subsequent light pulses. The variations of the illumination parameters produce controllable modulations of the vascular effects, phenomenon that could be therapeutically exploited through the variation of the used illumination fluence